Search Results (8,786)

Lung involvement in patients with leptospirosis is associated with a more complicated disease course. However, the demographic and clinical associations of lung involvement are incompletely defined, and its optimal management is uncertain. This retrospective study examined consecutive patients admitted to a referral hospital in tropical Australia, with laboratory-confirmed leptospirosis between January 2015, and June 2024. Lung involvement was defined as new lung parenchymal changes on chest imaging at any point during the patients’ hospitalisation. The demographics, clinical findings and clinical course of the patients with and without lung involvement were compared. The median (interquartile range (IQR)) age of the 109 patients was 39 (24–56) years; 93/109 (85%) were male. Lung involvement was present in 62/109 (57%), 55 (89%) of whom had no documented comorbidities. Patients with lung involvement received antibiotics later in their disease course than those without lung involvement (after a median (IQR) of 5 (4–6) versus 3 (2–5) days of symptoms, p = 0.001). Lung involvement was frequently associated with multi-organ failure: patients with lung involvement were more likely to require intensive care unit admission than patients without lung involvement (41/62 (66%) versus 15/47 (32%), p < 0.001). Overall, 30/109 (28%) satisfied criteria for acute respiratory distress syndrome (ARDS) and 26/109 (24%) developed pulmonary haemorrhage. Patients with lung involvement received cautious fluid resuscitation, vasopressor support and prompt initiation of additional supportive care—including mechanical ventilation, renal replacement therapy and extracorporeal membranous oxygenation—guided by the patients’ physiological parameters and clinical trajectory. All 109 patients in the cohort were alive 90 days after discharge. Life-threatening lung involvement was identified in the majority of individuals in this cohort and occurred in young and otherwise well individuals. However, in Australia’s well-resourced health system excellent outcomes can be achieved using a standard contemporary approach to the management of a patient with undifferentiated infection while a confirmed diagnosis of leptospirosis is awaited. Full article

The coronavirus disease 2019 (COVID-19) pandemic has revealed a close and multifaceted relationship between viral infection, systemic inflammation, and cardiovascular health. Among the cardiac complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), atrial fibrillation (AF)—especially new-onset atrial fibrillation (NOAF)—has emerged as a major determinant of disease severity and prognosis. Clinical studies and meta-analyses show that 5–10% of hospitalized COVID-19 patients develop AF, with markedly higher rates in critically ill individuals. Both pre-existing and NOAF are independently associated with increased risks of intensive care admission, mechanical ventilation, thromboembolic events, and mortality. The underlying mechanisms involve a combination of cytokine-mediated inflammation, endothelial dysfunction, microvascular injury, and dysregulation of the renin–angiotensin–aldosterone system (RAAS). Viral downregulation of angiotensin-converting enzyme 2 (ACE2) receptors contributes to myocardial fibrosis, while hypoxia, oxidative stress, and autonomic imbalance further promote electrical remodeling and arrhythmogenesis. Post-infectious studies indicate that atrial structural changes and autonomic dysfunction may persist for months, predisposing survivors to recurrent arrhythmias. Technological advances in telecardiology and digital medicine have provided new tools for early detection and long-term monitoring. Wearable electroencephalography (ECG) devices, implantable loop recorders (ILRs), and artificial intelligence (AI)-based diagnostic algorithms enable continuous rhythm surveillance and individualized management, improving outcomes in post-COVID patients. This review summarizes current evidence on the epidemiology, pathophysiology, clinical implications, and monitoring strategies of AF in COVID-19. It underscores the importance of integrating telemedicine and AI-assisted diagnostics into cardiovascular care to mitigate the long-term arrhythmic and systemic consequences of SARS-CoV-2 infection. Full article

Ferroptosis is a novel iron-sensitive subtype of regulated cell death (RCD), persisting under extreme lipid peroxidation and iron/redox imbalances. Unlike apoptosis, necroptosis, and pyroptosis, ferroptosis is a signaling-driven process mediated through iron metabolism imbalance, polyunsaturated fatty acid (PUFA) exceeding oxidation, and defects in its protective systems like Xc-/GSH/GPx4. Specifically, this review establishes that iron-driven ferroptosis is a central underlying pathomechanistic factor in a broad range of human diseases. Significantly, whether its modulation is therapeutic, it is entirely conditional on the specific disease context. Thus, its induction can provide a promising antidote for destructive cancer cells when conjoined with immuno-therapies to boost anticancer immunity. Conversely, iron-mediated ferroptosis suppression is a key factor in countering destructive changes in a whole range of degenerative and acute injuries. Current therapeutic approaches include iron chelators, lipid oxidation inhibitors, GPx4 activators, natural and active compounds, and novel drug delivery systems. However, against all odds and despite its intense therapeutic promise, its translation into a practical medicinal strategy faces many difficulties. Thus, a therapeutic agent specifically focused on its modulation is still lacking. The availability of selective biologic markers is a concern. The challenges in the direct pathologic identification of ferroptosis in a complex in vivo systemic scenario remain. Current avenues for its future development are pathogen infections, the discovery of novel regulating factors, and novel approaches to personalized medicine centered on its organ-level in vivo signatures. Full article

Stroke is the second-largest cause of death and disability worldwide, and many patients require intensive care for airway compromise, hemodynamic instability, cerebral edema, or systemic complications. This review summarizes key aspects of ICU management in both acute ischemic stroke (AIS) and hemorrhagic stroke (HS). Priorities are airway protection, oxygenation, individualized blood pressure targets, and strict control of temperature and glucose. Neurological monitoring and prompt management of intracranial pressure (ICP), together with timely surgical interventions (hemicraniectomy or hematoma evacuation), are central to acute care. Seizures are treated promptly, while routine prophylaxis is not recommended. Prevention of aspiration pneumonia, venous thromboembolism, infections, and other intensive care unit (ICU) complications is essential, along with early nutrition, mobilization, and rehabilitation. Prognosis and decisions about intensity of care require shared discussions with families and involvement of palliative services, when appropriate. Many practices remain based on observational data or extrapolation from other populations, underlining the need for stroke-specific clinical trials. Outcomes are consistently better when patients are managed in specialized stroke or neurocritical care units with a multidisciplinary treatment approach Full article

Background: COVID-19 caused by SARS-CoV-2 is an acute disease which may lead to severe systemic inflammation, causing multi-organ dysfunction and death. Studies indicated that thyroid-stimulating hormone (TSH) levels were lower when the infection was more severe. Methods: We conducted a retrospective study of 105 patients admitted from 2020 to 2023 to the University Clinical Centre in Katowice with a positive COVID-19 test. TSH levels, white blood cell count (WBC), platelet count (PLT), C-reactive protein (CRP), D-dimers, procalcitonin levels, lymphocyte count and percentage, and neutrophil-to-lymphocyte ratio (NLR) were evaluated. Results: The average age was 69.49 (SD 14.14) and the range was 36–95 years. A total of 53.2% of the population were male. After statistical analysis, lymphocyte count (p = 0.0038) correlated positively and NLR (p = 0.04682) correlated negatively with TSH level in COVID-19 patients, and PLT correlated positively with TSH level in the female population (p = 0.0384), while CRP (p = 0.81320), D-dimers (p = 0.974), WBC (p = 0.6862), Lymphocyte percentage (p = 0.1838), and procalcitonin (p = 0.906) did not reach statistical significance. Conclusions: TSH levels may be associated with lymphocyte count and NLR in patients with confirmed cases of SARS-CoV-2 infection, and with PLT in the female subgroup. Other evaluated inflammatory markers were not significant. These findings suggest that TSH has potential as a biomarker of disease severity, but further studies are needed to investigate this claim, and consideration should be given to other indicators of inflammation. Full article

The clinical features and outcomes of adult acute leukemia (AL)-associated hemophagocytic lymphohistiocytosis (AL-HLH) remain insufficiently characterized. We retrospectively analyzed 45 adult patients diagnosed with AL-HLH between December 2019 and June 2023. Among 746 AL patients, 45 developed HLH, with 40 developing acute myeloid leukemia (AML), 4 developing acute lymphoblastic leukemia (ALL), and 1 developing mixed-phenotype acute leukemia (MPAL). According to the ELN 2022 criteria, 16 (35.6%) had favorable, 3 (6.7%) had interediate, and 26 (57.7%) had poor risk. At the time of HLH onset, seven (15.6%) patients were in composite complete remission (CCR), and 38 (84.4%) were in non-CCR states; 25 (55.6%) patients were newly diagnosed before induction chemotherapy. The HLH-94/04-based regimens (etoposide and dexamethasone) with or without ruxolitinib achieved an ORR (overall remission rate) of 82.2% and a CR rate of 66.7%. After anti-leukemic therapy, 60% (27/45) of patients achieved CCR for leukemia (including patients in CCR at HLH onset and those achieving CCR after treatment). Hematopoietic stem cell transplantation (HSCT) independently predicted sustained remission. The estimated overall rates at 6 and 12 months after HLH diagnosis were 73.1% and 59.2%, respectively. Multivariate Cox analysis identified failure to achieve CCR for leukemia as the only independent adverse prognostic factor. AL-HLH is an uncommon but severe complication that predominantly occurs in AML patients with poor-risk cytogenetics or active disease. Early recognition, effective HLH control, and achievement of CCR in AL are crucial for improving patient prognosis. Full article

Background and Objectives: Upper respiratory tract infections are one of the most common reasons for outpatient admission. Acute pharyngitis is typically caused by viruses and is self-limiting but in up to 30% of cases, secondary bacterial infection may occur, requiring antibacterial treatment. In the face of growing antibacterial resistance due to inappropriate systemic antibiotic use, different topical therapy would have benefits. The objective of this study was to compare changes in throat and tonsillar mucous membrane bacterial density in patients with acute pharyngitis after a single exposure to a local antibacterial agent presented in different pharmaceutical forms—medicated lozenge, throat spray, or a solution for gargling. Materials and Methods: This was a non-interventional observational study that involved 90 adult outpatients with acute pharyngitis. Patients were prescribed to one of three options: medicated lozenges (containing dequalinium chloride and cinchocaine hydrochloride)—Treatment A; throat spray (containing streptocide soluble and norsulfazol-sodium)—Treatment B; or a powder, Furasol^® 100 mg (containing furagin soluble), for use as an external gargling solution—Treatment C. Throat swab culture was collected before and 20 min after the single exposure to the medication. Microbial testing was performed using a semi-quantitative quadrant streak plate method to assess bacterial density before and after exposure. Results: Four pathogenic agents were isolated from the swabs, with Staphylococcus aureus being the most prevalent. Overall, a reduction in post-exposure bacterial growth intensity was observed in 84.6% of the samples after Treatment C exposure, with a statistically significant difference from both Treatment B (57.1%, p < 0.05) and Treatment A (10%, p < 0.05). The difference was also significant between Treatment A and Treatment B. Conclusions: The findings showed that the throat gargling solution had more impact on mucous bacterial load compared to the throat spray and medicated lozenges in the patients with acute pharyngitis. Further research should address the effects of different pharmaceutical forms of the same antibacterial agent, where available. Full article

Objectives: Inappropriate antibiotic prescribing for acute upper respiratory tract infections (URTIs) is a significant problem in emergency departments (EDs) worldwide. In this study, we separately evaluated the effectiveness of physician feedback and patient education in reducing antibiotic prescribing for URTIs in the ED setting. Methods: We conducted a quasi-experimental study across four large adult EDs in Singapore from January 2021 to December 2023. After a baseline period (18 months), two EDs were randomly assigned to either implement physician feedback or patient education for six months (intervention period 1), and all EDs subsequently implemented both interventions in the next six months (intervention period 2). Hierarchical segmented logistic regression was used to assess the effectiveness of the interventions in reducing weekly antibiotic prescribing for URTIs. Results: In the two EDs that implemented physician feedback first, there was a significant decrease in the trend of weekly antibiotics prescribed (AOR 0.981 [95% CI (0.964, 0.998)]) compared to the last 6 months of the pre-intervention period. Adding patient education in the next phase (intervention period 2) did not further reduce the trend of weekly antibiotics prescribed. For the second group of two EDs that implemented patient education first, there was no significant reduction in the weekly antibiotic prescribing trend during intervention period 1. With the addition of physician feedback, a significant decline in the trend of weekly antibiotics prescribed was observed in intervention period 2 (AOR 0.921 [95% CI (0.903,0.940)]). Conclusions: Physician feedback alone can reduce antibiotic prescribing for URTIs in EDs. Further research is warranted to assess the effectiveness of patient education involving multi-modal educational channels co-created with patients. Full article

Accurate, efficient, and explainable modeling of the dynamics of acute respiratory infections (ARIs) remains, in many aspects, a significant challenge. While compartmental models such as SIR (Susceptible–Infected–Recovered) remain widely used for that purpose due to their simplicity, they cannot capture the complicated multiscale nature of disease progression which unites individual-level interactions affecting the initial phase of an outbreak and mass action laws governing the disease transmission in its general phase. Individual-based models (IBMs) offer a detailed representation capable of capturing these transmission nuances but have high computational demands. In this work, we explore hybrid and surrogate approaches to accelerate forecasting of acute respiratory infection dynamics performed via detailed epidemic models. The hybrid approach combines IBMs and compartmental models, dynamically switching between them with the help of statistical and ML-based methods. The surrogate approach, on the other hand, replaces IBM simulations with trained autoencoder approximations. Our results demonstrate that the usage of machine learning techniques and hybrid modeling allows us to obtain a significant speed–up compared to the original individual-based model—up to 1.6–2 times for the hybrid approach and up to ${10}^4$ times in case of a surrogate model—without compromising accuracy. Although the suggested approaches cannot fully replace the original model, under certain scenarios they make forecasting with fine-grained epidemic models much more feasible for real-time use in epidemic surveillance. Full article

Early-life infections can produce durable changes in immune function and behavior. We propose a mechanistic hypothesis positioning the mechanistic target of rapamycin (mTOR) as the link between peripheral inflammation and central nervous system dysfunction in pediatric post-infectious syndromes. Based on clinical, translational, and experimental literature, we outline a stepwise pathway. First, sustained mTOR activation skews T-cell and macrophage differentiation toward pro-inflammatory and autoimmune states. Second, endothelial mTOR signaling weakens tight junctions and increases vesicular transport, compromising blood–brain barrier integrity. Third, cytokines and sometimes autoreactive cells enter the brain and engage mTOR in microglia and neurons, driving neuroinflammation, impaired synaptic maintenance and plasticity, and neurotransmitter disruption. This framework accounts for features observed in Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and pediatric acute neuropsychiatry syndrome (PANS/PANDAS) and yields testable predictions on pathway activity and barrier permeability. It also motivates targeted interventions that modulate mTOR-related processes in immune and endothelial compartments and within neural circuits in children. So, this article aims to outline a mechanistic framework linking infection-driven mTOR activation to post-infectious neuropsychiatric syndromes. Full article

Dengue fever typically presents as a febrile illness, and acute pancreatitis has been reported as a rare complication. Limited evidence exists regarding clinical features, imaging findings, and outcomes, particularly on the distinction between acute interstitial pancreatitis and acute necrotizing pancreatitis. This systematic review was therefore designed in accordance with PRISMA guidelines (PROSPERO ID: CRD420250631013) in order to characterize the clinical spectrum of dengue virus (DENV)-associated acute pancreatitis by recollecting available case reports from PubMed, EMBASE, Scopus, MedRxiv, and BioRxiv Case reports and case series, which were included if they described laboratory-confirmed DENV infection and met the diagnostic criteria for acute pancreatitis. Seventy cases of DENV-associated acute pancreatitis were identified, mostly from Asia (78.6%) and South America (17.1%). Patients were predominantly male (62.9%), with a mean age of 31.6 years. Acute interstitial pancreatitis was more common (65.7%) than acute necrotizing pancreatitis (34.3%). Acute necrotizing pancreatitis was associated with leukocytosis, pancreatic collections, multiorgan and respiratory failure, prolonged hospital stay, and higher mortality (25.0% vs. 4.3% for acute interstitial pancreatitis). Overall, the case fatality was 11.4%, and survival analysis demonstrated significantly worse outcomes for acute necrotizing pancreatitis. In summary, clinicians should maintain awareness of this complication, as early recognition and appropriate management may improve outcomes. Full article

Background: Femoral neck fractures (FNFs) in the ageing population carry high risks of postoperative dislocation, with traditional total hip arthroplasty (THA) reporting rates up to 10%. Dual mobility THA (DM-THA) may provide enhanced stability, but evidence for third-generation implants like the Zimmer Biomet G7^® system remains limited. Methods: This retrospective cohort study evaluated 120 patients (mean age 71.6 years; 74% female) with acute displaced intracapsular FNF treated with DM-THA (2021–2023) using the G7^® system. Demographics, surgical details (cemented/uncemented stems), complications, and functional outcomes (Oxford Hip Score (OHS) at one year) were analysed against national benchmarks. Results: Zero dislocations and two peri-prosthetic fracture (0.8%, cemented stem) occurred. Thirty-day mortality was 0.8% (below national averages). Functional recovery was excellent (mean OHS: 41/48; 69% scoring ≥40). Surgical complications were minimal (one deep infection 0.8%). Medical complications (anaemia 6.6%, venous thromboembolism 4.2%) were significantly higher in high ASA groups (III-IV). Radiographs confirmed stable implants without loosening. Conclusions: The G7^® DM-THA system demonstrates exceptional stability and safety in FNF patients, with no dislocation risk and low peri-prosthetic fracture rates—even with cemented stems. These outcomes support its use in high-risk populations, though comparative studies with conventional THA are needed. Full article

Neutropenic patients with acute myeloid leukemia (AML) are at high risk for severe, multidrug-resistant infections. Sepsis due to carbapenem-resistant Pseudomonas aeruginosa (CRPA) in this population often leads to septic shock and acute respiratory distress syndrome (ARDS), with historically poor outcomes. CytoSorb™ hemoadsorption has been proposed as an adjunctive therapy for refractory septic shock, but evidence in hematologic malignancies remains limited. This report describes a 29-year-old male with newly diagnosed AML complicated by neutropenic fever, bacteremia due to CRPA, and subsequent hospital-acquired pneumonia progressing to ARDS. Despite multiple antibiotic regimens and aggressive intensive care management, including mechanical ventilation, prone positioning, and continuous renal replacement therapy (CRRT), the patient developed refractory septic shock with persistent lactic acidosis and elevated inflammatory markers. Early adjunctive CytoSorb hemoadsorption was initiated, guided by maximal CytoScore criteria, as part of a comprehensive supportive strategy. Following CytoSorb therapy, the patient demonstrated transient hemodynamic and biochemical improvement; however, profound neutropenia and multi-organ failure persisted. Microbiological clearance of CRPA was not achieved; given confirmed colistin susceptibility and unknown carbapenemase mechanism, a salvage combination of colistin plus ceftazidime–avibactam was employed. Transient hemodynamic improvement was observed after CytoSorb initiation; however, cytokine assays were not performed, and microbiological clearance was not achieved, precluding any mechanistic attribution to CytoSorb. This case highlights the complexity of managing CRPA sepsis and ARDS in neutropenic AML patients, and the challenges in attributing observed clinical improvement to CytoSorb therapy in the context of multiple simultaneous interventions. The absence of cytokine assays (e.g., IL-6, TNF-α) precludes any mechanistic attribution of observed changes to cytokine adsorption, and interpretation should remain descriptive rather than causal. Observed transient changes occurred amid simultaneous interventions (broad-spectrum antibiotics, CRRT, prone ventilation, corticosteroids, and filgrastim), precluding attribution to any single therapy, including CytoSorb. Given the fatal outcome and persistent CRPA positivity, the clinical impact of this observation is limited, and the generalizability of a single-case report is restricted. Cautious interpretation is warranted, and CytoSorb may be considered as part of a comprehensive care bundle rather than as a standalone solution. Alternative tetracycline-based combinations were reviewed but not adopted under our center’s salvage protocol for this XDR presentation. Future studies are warranted to clarify its clinical benefit and optimal timing in this population. Full article

Background: Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC), affects millions globally, with persistent symptoms impacting quality of life. This meta-analysis synthesizes prospective cohort studies to estimate the prevalence of Long COVID symptoms and identify risk factors. Methods: We systematically searched PubMed for prospective cohort studies (2020–2025) on Long COVID, focusing on prevalence and risk factors. Studies with ≥100 participants and follow-up ≥3 months were included. Data were extracted on symptom prevalence (e.g., fatigue, dyspnoea) and risk factors (e.g., sex, hospitalization). Random-effects models were used to pool prevalence and odds ratios (OR). Risk of bias was assessed using the Newcastle–Ottawa Scale (NOS). Results: Fourteen prospective studies (n = 168,679) were included. Pooled prevalence of Long COVID was 18.0% (95% CI: 12.5–23.5%, I² = 9.8%) among survivors followed for ≥6 months. Fatigue (41.0%, 95% CI: 33.2–49.4%) and dyspnoea (22.5%, 95% CI: 15.6–29.8%) were the most common symptoms. Female sex (OR = 1.52, 95% CI: 1.25–1.92) and prior hospitalization (OR = 2.35, 95% CI: 1.98–2.90) were significant risk factors. High heterogeneity (I² > 90%) was noted. Conclusions: Long COVID affects over one-fifth of SARS-CoV-2 survivors, with fatigue and dyspnoea persisting in many. Female sex and severe acute infection increase risk. Standardized definitions and longer follow-up are needed. Full article

The artificial breeding of fireflies is vital for supplementing natural populations. Unfortunately, mycosis is being observed with increasing frequency in the artificial breeding of fireflies, resulting in increased mortality. This study reports the identification of a microfungus that infects larval Pygoluciola sp., a species of semi-aquatic fireflies, during artificial breeding. Morphological and molecular analysis identified the fungi as Trichoderma koningiopsis (named as ZL01 strain). In addition, nystatin was selected out of five candidates as the optimal antifungal agent against T. koningiopsis ZL01, with a minimum inhibitory concentration of 25.00 μg/mL. Acute oral and contact in vivo toxicity tests on larval Pygoluciola sp. confirmed the safety of nystatin. Furthermore, compared to a Pygoluciola sp. larval population infected with T. koningiopsis ZL01, nystatin treatment increased the survival rate of larvae by twofold (spray administration) and threefold (drip administration) at the end of a nine-day artificial breeding experiment. These findings indicate that nystatin could be used as a potential antifungal agent to control mycosis in artificially bred fireflies. This study was the first to document the infection of semi-aquatic fireflies by pathogens and provide a corresponding treatment strategy. Full article